Polymorphism rs6265 near BDNF gene is associated with blood pressure in Chinese children and adolescents

Abstracts

The Beijing Child Blood Pressure Study (BBS), which was a crosssectional survey for the prevalence of hypertension in children aged 6–18 years, was conducted in 1987. 936 subjects (492 males, 52.6%) from the BBS cohort were followed up in 2010, with their birth information recalled. Height, weight, systolic blood pressure (SBP), diastolic blood pressure (DBP), brachial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (cIMT) were measured. Childhood hypertension was defined by SBP and/or DBP ≥95th percentile for age and gender. Adult hypertension was diagnosed as SBP ≥140 mm Hg and/or DBP ≥90 mm Hg or the subjects taking anti-hypertension drugs presently. Age, gender, premature delivery and breast feeding within the first 4 months of infant's age were adjusted. Results: There was negative association between birth weight and SBP in females. After adjusting for body mass index (BMI), the association was strengthened in childhood, and weakened in adulthood. Females with low birth weight (LBW, b2500 g) have higher risk of hypertension both in child and adulthood than those with normal birth weight (≥2500–b4000 g). Four groups were divided by birth weight and current weight. Compared with normal group, the odds ratios (95% CI) of predicting adult hypertension risk were increased across LBW group, obese group, and LBW plus obese group. Moreover, birth weight was negatively associated with baPWV, and positively associated with cIMT in adult females after adjusting for current BMI, hypertension and other factors. Conclusions: Birth weight is inversely associated with SBP in females both in childhood and adulthood. LBW increases the risk of childhood hypertension independent of obesity. LBW amplifies the effect of obesity on hypertension in adulthood. doi:10.1016/j.ijcard.2011.08.667 0239 Association between obesity in childhood and hypertension incidence: A prospective cohort study YINKUN YANa, HONG CHENGa, JIALI DUANb, YULIANG ERb, JIE MIa a Capital Institute of Pediatrics, Beijing, China b Beijing Centers for Diseases Control and Prevention, Beijing, China Objective: To explore the association between obese level as well as the level of change in childhood and hypertension incidence. Methods: A perspective cohort study was conducted. As part of Beijing Child and Adolescent Metabolic Syndrome (BCAMS) study, 2189 non-hypertensive children aged 6–16 years at school were followed up in 2010. In this study, height, weight, waist circumference (WC) and blood pressure was measured at follow-up, and body mass index (BMI) and WC was respectively used to assess overweight/obesity and abdominal obesity. Results: The total hypertension incidence of 1184 subjects during 6 years follow-up was 19.9%. The hypertension incidence in male (23.2%, 149/643) was higher than in female (16.1%, 87/541) (x2 = 9.257, P = 0.002). The hypertension incidence of non-overweight, overweight and obese (BMI) children at baseline was, respectively, 8.7% (45/519), 19.3% (35/181), 32.4% (156/484) (x2trend = 9.332, P b 0.001), and the incidence of non-obese and obese (WC) children at baseline was respectively 10.3% (63/613), 30.7% (173/567) (x2 = 77.753, P b 0.001). Multivariable OR (95% CI) of incident hypertension in the baseline obesity group was higher than the control (BMI, OR = 4.9, 95% CI: 3.4–7.0; WC, OR = 3.9, 95% CI: 2.8 –5.3). The hypertension incidence increased with the follow-up BMI/WC level, based on the same baseline level (P b 0.005). The hypertension risk increased to respectively 0.21 and 0.07 times with elevation of baseline BMI level by 1 kg/m2 and WC level by 1 cm, and OR (95% CI) are respectively 1.21 (1.16–1.26) and 1.07 (1.05–1.09). Similarly the hypertension risk increased respectively to 0.16 and 0.05 times with the elevation of BMI level change by 1 kg/m2 and 1 cm, and

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OR (95% CI) are respectively 1.16 (1.11–1.22) and 1.05 (1.03–1.07). Conclusion: Both BMI/WC levels and the level change are associated with the hypertension incidence. doi:10.1016/j.ijcard.2011.08.668 0242 Childhood hypertension predicts risk of target organ damage in adulthood YAJUN LIANGa,b, DONGQING HOUa, YUEHUA HUa, JUNTING LIUa, JIE MIa a Department of Epidemiology, Capital Institute of Pediatrics, Beijing, China b School of Public Health, Jining Medical University, Jining, Shandong, China Objectives: Cardiovascular disease in adulthood is proved to extend back to childhood. This prospective cohort study aimed to observe the predictive value of childhood hypertension on target organ damage (TOD) in adulthood. Methods: 1126 participants (aged 6–18 years old, with mean age of 11.3 ± 3.7 years) from “Beijing Children and Adolescents Blood Pressure Study” in 1987 were included and divided into 5 sub-cohorts (6 years, 9 years, 12 years, 15 years, and 18 years). In 2010, prospective cohort study was conducted to follow up these participants in their adulthood (aged 29–41 years old, with mean age of 34.5 ± 3.6 years). Both in childhood and in adulthood, height, weight and blood pressure (BP) were measured, and demographic data and related factors of hypertension were collected through questionnaire. In adulthood, subclinical indexes of TOD were also assessed, including brachial-ankle pulse wave velocity (baPWV) to assess artery stiffness, carotid–femoral pulse wave velocity (cfPWV) to assess aorta stiffness, left ventricular mass index (LVMI) and relative wall thickness (RWT) to assess left ventricular hypertrophy (LVH), and microalbuminuria. Results: baPWV, cfPWV, LVMI and RWT in adulthood increased with the increase of BP values in childhood (P b 0.05). Hypertensive children were observed to have significantly higher prevalence of artery stiffness and LVH in adulthood than their counterparts with normal BP in childhood (P b 0.01). After adjustment of related confounding factors, hypertensive children in the sub-cohort of 9 years old were at higher risks of developing artery stiffness and LVH in adulthood compared with their normotensive counterparts. However, no significant association was observed between childhood hypertension and aorta stiffness and microalbuminuria in adulthood. Conclusion: Childhood hypertension was a good predictor of artery stiffness and LVH in adulthood. Among hypertensive children, BP should be effectively controlled from 9 years old to prevent artery stiffness and LVH in their adulthood. doi:10.1016/j.ijcard.2011.08.669 0247 Polymorphism rs6265 near BDNF gene is associated with blood pressure in Chinese children and adolescents BO XIa,b, LIJUN WUa, MEIXIAN ZHANGa, YUE SHENa, XIAOYUAN ZHAOa, HONG CHENGa, DONGQING HOUa, XINGYU WANGc, JIE MIa a Capital Institute of Pediatrics, Beijing, China b Shandong University, Jinan, China c Beijing Hypertension League Institute, Beijing, China Objective: A recent genome-wide association study (GWA) suggested that polymorphism rs6265, near brain-derived neuro-

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Abstracts

trophic factor (BDNF) gene, was associated with BMI and obesity in Caucasian adults. We examined the association of rs6265 with blood pressure and hypertension in Chinese children and adolescents. Methods: A total of 3091 children and adolescents (age 6–18 years), including 621 hypertensive and 2470 normal blood pressure (BP) subjects were recruited. Polymorphism rs6265 was genotyped by Taqman 7900 Sequence Detection System. Results: After adjustment for age, gender, pubertal stage and body mass index, polymorphism rs6265 was significantly associated with both systolic BP (β = 0.71, 95% confidence interval (CI) 0.19–1.22, P = 0.007) and diastolic BP (β = 0.58, 95% CI 0.16–0.99, P = 0.007). Polymorphism rs6265 was also significantly associated with hypertension risk under an additive genetic model with the covariates adjustment (odds ratio = 1.15, 95% CI 1.00–1.33, P = 0.049). Conclusions: To our knowledge, this was the first study investigating the association of polymorphism rs6265 with blood pressure and hypertension. BDNF gene might be implicated in the regulation of BP in Chinese children and adolescents. However, further large scale studies are required to confirm the association in Chinese and other ethnic populations. doi:10.1016/j.ijcard.2011.08.670 0361 Hypertension in children and adolescents within community and its risk factors

Objective: Bridelia ferruginea Benth (Euphorbiaceae) is used traditionally for the treatment of hypertension and as a diuretic. The diuretic activity of this substance has not been investigated in scientifically controlled studies. The aim of the present study was to evaluate the effect of aqueous extract of Bridelia ferruginea stem–bark on renal function in rats after acute administration. Methods: Male Wistar rats were used in all experiments. After 18 h of total diet, the rats received 50 mL/kg of distilled water orally before treatments. To determine its influence on renal function the single dose of the aqueous extract of Bridelia ferruginea (10 mg/kg) or the reference drug, furosemide (10 mg/kg) were administrated intraperitoneally to the rats. The concentration of urinary urea and creatinine was also investigated. The urea and creatinine in plasma were determined and the glomerular function was measured by creatinine and urea clearance. Results: Intraperitoneal administration of aqueous extract of Bridelia ferruginea at the dose of 10 mg/kg produced a significant increase in urinary excretion of creatinine (P b 0.01 compared to control) and creatinine clearance (P b 0.05 compared to control) in rats. The urinary urea and plasma urea were not affected by the aqueous extract of Bridelia ferruginea. Urinary urea and urea clearance were also affected by furosemide. Conclusion: These results suggest that the glomerular function was not affected by the aqueous extract of Bridelia ferruginea after 24 h. These findings support the traditional use of this plant. doi:10.1016/j.ijcard.2011.08.672

XIAOMEI ZHANG, JINGHUI SUN The First Hospital of Jilin University, Changchun, China Objective: To investigate prevalence and characteristics of hypertension in children and adolescents in the community and explore its related risk factors. Methods: Randomly selected one district that includes 21 communities in Changchun of Jilin Province, China. Hypertensive patients in these communities under 18 years were recruited into the study. Results: Patients diagnosed were 441 cases (male 306 and female 135, mean age 11.46 ± 3.25, from 4 to 17 years old), 260 cases (58.96%) were essential hypertension, and 181 cases (41.04%) were secondary hypertension. The prevalence of essential hypertension was 0.27% (260/97900). The latest National Health and Nutrition Examination Survey (NHANES III) was used to calculate the age-dependent z scores. Systolic blood pressure (BP) z score did not correlate with birth weight and gestational age, but did correlate with age of maternal pregnancy (r = 0.256, P b 0.001), maternal pre-pregnancy body mass index (BMI) (r= 0.471, P b 0.001) and child BMI z score (r= 0.218, P b 0.001). Diastolic BP z score positively correlated with birth weight (r = 0.176, P = 0.005), gestational age (r = 0.183, P b 0.005), BMI z score (r = 0.206, P b 0.001) and maternal pre-pregnancy BMI (r= 0.194, P = 0.002). Conclusions: Children and adolescents with essential hypertension who had not been diagnosed in the community were very many, and prevention and treatment hypertension should be focused on the community. Essential hypertension in children and adolescents did correlate with age of maternal pregnancy, maternal prepregnancy BMI, child BMI z scores, gestational age and birth weight. doi:10.1016/j.ijcard.2011.08.671

Kidney 0018 Effects of Bridelia ferruginea Benth. (Euphorbiaceae) aqueous extract on renal function in the rat BI SEMI ANTHELME NENE, OUGA STANISLAS ZAHOUI, TIANGA YAYA SORO University of Cocody-Abidjan, Abidjan, Cote d'Ivoire

0039 Comparing antihypertensive effect and plasma CsA concentration between amlodipine and valsartan regimen in hypertensive renal transplant patients with CsA therapy ZHIJUN HUANG, JINGJING CAI, GUOPING YANG, HONG YUAN The Center of Clinical Pharmacology of the Third Xiangya Hospital, Changsha, Hunan, China Objective: The aim of the present study is to evaluate the effect of amlodipine and valsartan on blood pressure control in renal transplant patients and to analyze the correlation between CYP3A5 or MDR1 genotype and the antihypertensive effect of these two regimens. Methods: One hundred and fifty renal transplant patients with stage 1 or 2 hypertension were enrolled in the trial. Patients were randomly assigned to amlodipine or valsartan. Metoprolol was added if blood pressure was not under control after 4 weeks. At 24 weeks of the trial, blood pressure, plasma levels of cyclosporin A (CsA), CYP3A5 and MDR1 genotypes were analyzed. Result: The demographic features and the baseline blood pressure were similar between these two groups. At 24 weeks of the trial, the reduction of systolic blood pressure was similar between the amlodipine and valsartan groups. However, the reduction of diastolic blood pressure was significantly greater in the amlodipine group compared to the valsartan group (− 12.2 ± 2.4 mm Hg vs −6.5 ± 2.0 mm Hg, P b 0.05). The plasma level of CsA at 2 h of medication (C2) was significantly higher in the amlodipine group than that in the valsartan group (314.4 ± 20.17 ng/mL vs 261.4 ± 16.79 ng/mL, P b 0.05). The reduction of diastolic blood pressure was greater in the subjects with CYP3A5*3/*3 variant than those with CYP3A5*1/*1 variant (−13.5 ± 1.99 mm Hg vs − 8.7 ± 1.6 mm Hg, P b 0.05). Subjects with a CYP3A5*3*3/MDR1 T genotype had better response to amlodipine in blood pressure reduction compared to those with other genotypes. Conclusion: The present study demonstrated that amlodipine produced a greater reduction of DBP than valsartan although both amlodipine and valsartan resulted in a satisfactory control of blood pressure in patients with renal transplantation. Administration of amlodipine significantly increased the plasma concentration of CsA, and its effects on blood